Study Identifies OCT Biomarker for Assessing Photoreceptor Integrity in DR

Researchers have observed reduced outer retinal reflectivity in patients with diabetic retinopathy (DR)—even those without clinical signs—compared to healthy controls. A new study published earlier this week in the journal Eye is the first to assess these changes across different DR severities. The analysis revealed an association between more advanced disease stages and decreased photoreceptor integrity, with the most significant differences noted in the outer macular ring and peripapillary region. Relative ellipsoid zone reflectivity, previously identified as a biomarker for AMD and macular telangiectasia, may also assist in DR staging, study suggests. These images from the study show: Infrared fundus images (A, B) with yellow lines indicating the scanned areas; horizontal (C) and vertical (D) OCT B-scans with yellow boxes marking the regions used for retinal reflectivity measurements at various distances from the foveal center and at the peripapillary region in the horizontal scan; and representative reflectivity profiles of the horizontal (E) and vertical scans (F). The first peak corresponds to the external limiting membrane and the second peak to the ellipsoid zone. Photo: Huber KL, et al. Eye. March 3, 2026. Click image to enlarge. In the exploratory cross-sectional study, 64 eyes of 44 patients were imaged using high-resolution spectral-domain OCT. The cohort consisted of 17 eyes with no DR, 33 eyes with nonproliferative DR (NPDR) and 14 eyes with proliferative DR (PDR). Relative ellipsoid zone reflectivity (rEZR)—characterized as the ratio between the ellipsoid zone and the external limiting membrane reflectivity—was measured across multiple locations, particularly in regions defined by the Early Treatment Diabetic Retinopathy Study grid.The results demonstrated significant variations in rEZR, particularly highlighting a pronounced decline in reflectivity associated with more severe forms of DR. In the outer macular ring, the average rEZR of eyes affected by PDR was significantly lower compared to those without DR and those with NPDR. This trend was mirrored in measurements taken from the total area, where eyes in the PDR category exhibited markedly reduced rEZR compared to eyes with no DR or NPDR.Assessments of the peripapillary region also echoed these findings, indicating a considerable decrease in rEZR for NPDR compared to no DR and for PDR relative to no DR. In contrast, the results showed no significant differences between groups in the foveola, central 1mm or inner macular ring.“Our analysis showed that rEZR significantly varies across different foveal eccentricities, with the highest reflectivity observed in the perifoveal region with a decline towards the fovea,” the researchers explained in their paper. “This pattern may reflect regional differences in mitochondrial distribution within the EZ, with increasing ellipsoid volume at greater eccentricities from the foveal center.” They also noted that rod density in the perifoveal region is significantly greater than cone density, and previous work has shown that early DR is marked by predominant damage to rod photoreceptors.Together, these findings point to the potential of rEZR as a reliable and quantitative biomarker for assessing photoreceptor integrity in DR patients. This OCT-based assessment “has been established in recent studies of age-related macular degeneration and macular telangiectasia, where it has proven to be a reliable imaging biomarker for detecting photoreceptor damage, correlating with both disease severity and functional decline.” While some studies have investigated rEZR as a biomarker for DR, this is the first to evaluate the measurement across different severities of disease and to suggest that “advanced stages of DR are associated with a more pronounced reduction of the rEZR, particularly in the outer macular and peripapillary regions.”Click here for the journal source. Huber KL, Himmel D, Steiner I, et al. Evaluation of photoreceptor integrity in diabetic retinopathy using high-resolution optical coherence tomography. Eye. March 3, 2026. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.